The DF/HCC Lung Cancer Program will continue to generate new discoveries in host susceptibility, exposure to pulmonary carcinogens, epidemiology, and pathogenesis of lung cancer, and will apply this information to develop novel prevention and therapeutic strategies to prevent lung cancer and improve the therapies of patients at risk or with lung cancer. The Lung Cancer Program was approved at the time of the last CCSG review in 2005 and was awarded a merit score of excellent to outstanding. The Lung Cancer Program has 60 members representing ten departments of HMS and' HSPH and six member institutions. Members have a broad range of expertise in epidemiology, molecular epidemiology, genetics, cancer biology, clinical trials and outcomes analyses. Program members have had neariy 692 publications in the last five years. Of these 692, 30% are intra-programmatic, 47% are inter-programmatic and 33% are inter-institutional peer-reviewed manuscripts. DF/HCC provides a mechanism for these Lung Cancer Program investigators to develop an interconnected program of population, basic and clinical scientists based on overiapping and interactive areas of expertise. The Lung Cancer Program has nearly $13 million in external support, including more than $6 million in NCI funding and $2.3 million in other peer-reviewed support. The specific aims for the next five years are to: 1) Identify germline polymorphisms and determine their role in the susceptibility, pathogenesis and response to therapy and survival in lung cancer; 2) Define pathogenic mechanisms underiying the development of lung cancer; and 3) Exploit the discoveries in pathogenesis to develop novel therapeutic approaches to thoracic malignancies.